顺铂临床疗效和毒性相关基因多态性研究进展

Research advances on the influence of gene polymorphism on clinical efficacy of cisplatin

顺铂是临床上治疗乳腺癌、膀胱癌等实体瘤的常用化疗药物,但是随着DNA修复、解毒、排泄等过程的发生,顺铂及其代谢产物的疗效及毒副作用个体差异较大,越来越多证据支持基因多态性对顺铂疗效及毒副反应的预测作用。该文从核苷酸切除修复途径、肝脏解毒及肾脏排泄过程的基因多态性进行综述,结合亚裔人群的突变概率,分析影响顺铂临床疗效及毒性相关的基因多态性,其中rs25487、rs11615、rs316019作为亚裔中突变率较高的单核苷酸多态性,在制定化疗方案前进行基因多态性检测,将有利于减少毒副作用,提高顺铂的临床疗效,为制定顺铂个体化给药提供借鉴意义。

Cisplatin is a common chemotherapeutic agent for treating such solid tumors as breast and bladder cancers.Its therapeutic responses and toxic/side effects vary greatly amongst individuals due to DNA repair,detoxification and excretion.There is growing evidence that genetic polymorphisms play a predictive role in efficacy and adverse reactions of cisplatin.This review focused upon gene polymorphisms involved in nucleotide excision repair pathways,liver detoxification and kidney elimination processes.In conjunctions with mutation probabilities in Asian populations,gene polymorphisms associated with cisplatin were analyzed in terms of clinical efficacy and toxicity.Among them,rs25487,rs11615 and rs316019 are SNPs with higher mutation rates in Asians.Detecting gene polymorphisms before formulating chemotherapy regimens helps to minimize toxic/side effects and boost the clinical efficacy of cisplatin.It provided references for individualized dosing of cisplatin in clinical practices.